Cystic Lesions of the PancreasMatthew A. Zarka

Division Chair: Anatomic Pathology Mayo Clinic Arizona

ROSE Rapid Onsite Evaluation

• ROSE has been shown to be effective in optimizing the yield and efficiency of EUS-FNA

• Only solid tumors should be asked for ROSE

• Like frozen and intra-operative consultation, definitive diagnosis should NOT be demanded on ROSE

• Staffing, time, and cost constraints limit availability

Pancreatic Cyst Terminology

• Unsatisfactory (Reason)

• Negative (Consider descriptive)

• Cystic contents: Mucinous epithelium is not identified

• Negative for high grade dysplasia or malignancy, no cyst contents

• Debris/inflammatory cells present without mucinous epithelium c/w pseudocyst

• Atypical

• Mucinous epithelium present, no evidence of high grade dysplasia

• of uncertain origin

• c/w mucinous neoplasm (most likely IPMN)

• C/W serous cystadenoma

• Suspicious for malignancy

• Mucinous epithelium present with at least high grade dysplasia/CIS

• Abnormal epithelium suspicious for invasiv adenocarcinoma

• Positive for malignancy

• Adencarcinoma

Pancreatic Lesions• Solid

• Chronic pancreatitis

• Ductal adenocarcinoma

• Acinar cell carcinoma

• Pancreatic endocrine neoplasm (PEN)

• Solid pseudo-papillary tumor (SSPT)

• Pancreatoblastoma

• Metastasis

• Cystic

• Pseudocyst

• Serous cyst

• Mucinous cyst (MCN and IPMN)

• Cystic degeneration of typically solid tumors

• PEN

• SSPT

• other

• Other more rare cysts

• Simple cysts

• Lymphoepithelial cyst

• Peripancreatic cysts

EUS-Fine Needle Aspiration

Transgastric: body and tailTransduodenal: head

• Non-neoplastic

• Pseudocyst

• Retention cyst

• Congenital cyst

• Foregut cyst

• Endometriotic cyst

• Cystic nonepithlial neoplasms

• Lymphangioma

• Hemangioma

• Secondarily cystic solid neoplasms

• Ductal adenocarcinoma

• Endocrine neoplasms

• Acinar cell neoplasms

• Solid-pseudo papillary neoplasm

Cysts of the pancreas

• Primarily cystic epithelial neoplasms

• Serous cystadenoma

• Mucinous cystic

• w/ low grade dysplasia

• w/ high grade dysplasia

• w/ invasive carcinoma

• Intraductal papillary mucinous neoplasm (IPMN)

• w/ low grade dysplasia

• w/ high grade dysplasia

• w/ invasive carcinoma

• Secondarily cystic solid neoplasms

• Ductal adenocarcinoma

• Endocrine

• Acinar cell

• Solid pseudo papillary

Cysts of the pancreas

EUS: Normal Stomach

• Thick mucus

• Small clusters

• Apical mucin

• Cell types

• Mucinous, parietal, chief cells

Duodenum

• Thin mucus

• Large tissue fragments

• Goblet cells

• Terminal bars

Pancreas

• Ductal cells

• Acinar cells

• Islet cells

International Guidelines for Pancreatic Cysts2012 Version

Pancreatic pseudocyst• Clinical

• Age: All ages (pancreatitis – older)

• Males>Females

• Tail more common

• 2-30 cm

• Gross: fibrous, necrortic wall

• Chemistry: high amylase and lipase, low CEA

Adsay NV. ModPathol (2007): 20:S71-S93

Pancreatic pseudocyst• Hypocellular and lack

epithelial cells

• Nonspecific cyst

• Necrosis, protein debris, inflammation, cholesterol crystals, and etc.

Serous cystadenoma• Clinical

• Gender: more common in women than men (7:3)

• Older (average 61-68)

• Location: anywhere

• Symptoms: abdominal pain and weight loss

• Site predilection: None, maybe heaad

• Prognosis: vast majority benign

• Gross: Numerous tightly packed small cyst and stellate scar; sponge-like

• Chemistry: low amylase and CEA

Adsay NV. ModPathol (2007): 20:S71-S93

Serous Cystadenoma: Cytology• Scant cellularity

• Histiocytes and histiocytes with hemosiderin common

• Flat sheet of cuboidal, bland, serous-type epithelium

• are not often present

• Lining cells with bland, centrally located nuclei, and may have nuclear grooves

• mimic benign mesothelial cells

Cytology – Low diagnostic accuracy

All histology confirmed SCA (n=21)

CT confirmed 3/12 (25%)

Histiocytes present 16/21 (76%)

Histiocytes with hemosiderin 11/21 (52%)

GI contamination 7/15 (47%)

SCA cells 5/21 (24%)

Prospectively Dx 1/21 (5%)

Belsley et. Al. Cancer (Cytopathology), 104:102-110, 2008

Mucinous Cystic Neoplasm• Gender: much more common

in women than men

• Age: mean age at diagnosis – 50

• Location: Tail > head

• Gross: Thick fibrous wall, multicystic; usually larger than 2cm

• Lined by ovarian stroma, septa may CA++

• Chemistry: low amylase, high CEA

Adsay NV. ModPathol (2007): 20:S71-S93

Mucinous cystic neoplasm: cytology• Thick mucous, if

present, extremely helpful

• Low cellularity

• Flat sheet or single mucous cells

• Ovarian-type stroma often absent

• Cytologic atypia depend on differentiation

• Cytology often underestimate the final histologic grade Pitman et al. Cancer Cytopathol. 2010:1181-13

Cooperative Pancreatic Cyst StudyBrugge, Gastroenterol 2004

Is this a mucinous cyst?

Neoplastic mucin or GI mucin?

If there are abundant “gut” epithelium, be careful!

Intraductal Papillary Mucinous Neoplasm (IPMN)• Clinical

• Male >> Female

• Mean age 68

• Location: Head (89%)

• Gross: Localized, multicentric, imp. to document of pancreatic ductal system

• Cystically dilated ducts containing mucin with various degrees of atypia

• Chemistry: High amylase, high CEA

• Imaging: communicate with pancreatic duct system – mucin oozing from the ampulla of Vater

Intraductal Papillary Mucinous Neoplasm: Cytology

• Thick mucus

• Papillary groups

• Low vs high cellularity

• Goblet cells

• Atypia

IPMN - Cytology

Stelow Michaels Layfield

Thick mucus 18/18 10/11 10/13

Papillary 3/18 5/11 8/13

Low cellularity 9/18 4/11 5/13

High cellularity 9/18 7/11 8/13

Goblet cells 6/18 N/A N/A

Atypia 3/18 7/11 8/13

IPMN – Triple Test

• Clinical-EUS: Thick mucin and cystic dilated duct system

• Radiographic: Cyst communicate with pancreatic duct

• Cytology: Mucinous neoplasm

Text

Adenocarcinoma• Major criteria

• Nuclear overlap and crowding

• Nuclear contour irregularity

• Chromatin clearing or clumping

• Minor criteria

• Single epithelial cells

• Necrosis, mitosis

• Nuclear enlargment

Acta Cytol, 1995; 39:1-10

Cystic Neuroendocrine Neoplasms

• Rare; 5-10% of pancreatic neoplasms

• Cyst formation not due to necrosis in contrast to cystiic adenocarcinoma

• Usually unilocular; up to 25 cm

Cystic Neuroendocrine Neoplasms: Cytology• Cellularity: varies

• Loose aggregate and single cell pattern

• Monomorphic appearance; some cells out of proportion to others

• Plasmacytoid, bi-nucleate

• Salt and pepper chromatin

• Pink granules of air dry

• Synaptophysin +

Ki-67 Matters

Ekeblad S et al. Clin Cancer Res 2008;14:7798-7803

Ki-67 < 2%

Ki-67 ~30% (Neuroendocrine CA)